Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). We achieve a long-lasting (>24 h) torpor-like state in mice via closed-loop feedback control of ultrasound stimulation with automated detection of body temperature. Ultrasound-induced hypothermia and hypometabolism (UIH) is triggered by activation of POA neurons, involves the dorsomedial hypothalamus as a downstream brain region and subsequent inhibition of thermogenic brown adipose tissue. Single-nucleus RNA-sequencing of POA neurons reveals TRPM2 as an ultrasound-sensitive ion channel, the knockdown of which suppresses UIH. We also demonstrate that UIH is feasible in a non-torpid animal, the rat. Our findings establish UIH as a promising technology for the noninvasive and safe induction of a torpor-like state.
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http://dx.doi.org/10.1038/s42255-023-00804-z | DOI Listing |
ACS Nano
September 2024
Wyss Institute for Biologically Engineering at Harvard University, Boston, Massachusetts 02215, United States.
Achieving a reversible decrease of metabolism and other physiological processes in the whole organism, as occurs in animals that experience torpor or hibernation, could contribute to increased survival after serious injury. Using a Bayesian network tool with transcriptomic data and chemical structure similarity assessments, we predicted that the Alzheimer's disease drug donepezil (DNP) could be a promising candidate for a small molecule drug that might induce a torpor-like state. This was confirmed in a screening study with tadpoles, a nonhibernator whole animal model.
View Article and Find Full Text PDFbioRxiv
March 2024
Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 455 Main Street, Cambridge, MA 02142, USA.
Torpor and hibernation are extreme physiological adaptations of homeotherms associated with pro-longevity effects. Yet the underlying mechanisms of how torpor affects aging, and whether hypothermic and hypometabolic states can be induced to slow aging and increase health span, remain unknown. We demonstrate that the activity of a spatially defined neuronal population in the avMLPA, which has previously been identified as a torpor-regulating brain region, is sufficient to induce a torpor like state (TLS) in mice.
View Article and Find Full Text PDFNat Metab
May 2023
Department of Biomedical Engineering, Washington University in St. Louis, Saint Louis, MO, USA.
Torpor is an energy-conserving state in which animals dramatically decrease their metabolic rate and body temperature to survive harsh environmental conditions. Here, we report the noninvasive, precise and safe induction of a torpor-like hypothermic and hypometabolic state in rodents by remote transcranial ultrasound stimulation at the hypothalamus preoptic area (POA). We achieve a long-lasting (>24 h) torpor-like state in mice via closed-loop feedback control of ultrasound stimulation with automated detection of body temperature.
View Article and Find Full Text PDFCells
April 2021
School of Biological Sciences & Institute for Global Food Security, Queens University Belfast, Belfast BT9 5DL, UK.
The development of the Artemis programme with the goal of returning to the moon is spurring technology advances that will eventually take humans to Mars and herald a new era of interplanetary space travel. However, long-term space travel poses unique challenges including exposure to ionising radiation from galactic cosmic rays and potential solar particle events, exposure to microgravity and specific nutritional challenges arising from earth independent exploration. Ionising radiation is one of the major obstacles facing future space travel as it can generate oxidative stress and directly damage cellular structures such as DNA, in turn causing genomic instability, telomere shortening, extracellular-matrix remodelling and persistent inflammation.
View Article and Find Full Text PDFLife Sci
February 2019
Russian Foundation for Advanced Research, Russia.
Aims: To initiate a state of artificial torpor we suggested a pharmacological multi-targeting strategy for simulation of the physiological pattern of natural hibernation including a significant reduction in heart rate, respiratory rate, body temperature and oxygen consumption as well as a decline in brain activity known as torpor.
Materials And Methods: We have developed a composition which initiates a pharmacologically induced torpor-like state (PITS-composition), made up of eight therapeutic agents, inert gas xenon and lipid emulsion served as a drug vehicle.
Key Findings: After a single intravenous injection to rats, PITS-composition causes a rapid decline in heart rate followed by a steady decrease in body temperature from about 38.
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